Scientists Have Successfully Developed A 3-D Brain Organoid

The U.S. Department of Health and Human Services (HHS) has called regenerative medicine the “next evolution in health care,” and scientists like Dr. Anthony Atala hope with its potential to heal, the field will revolutionize health care. "We have many challenges to meet, but are optimistic about the ability of the field to have a significant impact on human health,” the director of Wake Forest Institute for Regenerative Medicine (WFIRM) said. “We believe regenerative medicine promises to be one of the most pervasive influences on public health in the modern era.”

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With many firsts under their belts, the more than 300 scientists at Wake Forest Institute for Regenerative Medicine (WFIRM), where Atala is director, are working to translate the science of regenerative medicine into clinical therapies. These scientists hail from the fields of biomedical and chemical engineering, cell and molecular biology, biochemistry, pharmacology, physiology, materials science, nanotechnology, genomics, proteomics, surgery and medicine. Atala is a urologist.

Most recently, scientists at WFIRM developed a 3-D brain organoid that could have potential applications in drug discovery and disease modeling. “This is the first engineered tissue equivalent to closely resemble normal human brain anatomy, containing all six major cell types found in normal organs including, neurons and immune cells,” Atala said.

In a study published in May in Scientific Reports, of which Atala was the senior author, WFIRM researchers reported that their "3-D organoids promote the formation of a fully cell-based, natural and functional barrier - the blood-brain barrier - that mimics normal human anatomy."

The blood-brain barrier is a semipermeable membrane that separates the circulating blood from the brain, protecting it from foreign substances that could cause illness or injury. According to WFIRM, their discovery is important because “the model can help to further understanding of disease mechanisms at the blood-brain barrier, the passage of drugs through the barrier, and the effects of drugs once they cross the barrier.”

“Using an engineered tissue model provides a platform that can be used to understand the fundamental principles at play with the blood-brain barrier and its function, as well as the effects of chemical substances that cross it,” said Goodwell Nzou, a Ph.D. candidate at WFIRM who co-authored the paper.

Atala said the development of the model opens the door to speedier drug discovery and screening, both for neurological conditions and for diseases like HIV where pathogens hide in the brain and avoid current treatments that cannot cross the blood brain barrier. It may also allow for disease modeling of neurological conditions such as Alzheimer’s disease, multiple sclerosis and Parkinson’s disease so that researchers can better understand their pathways and progression, he said.

“The shortage of effective therapies and low success rate of investigational drugs are due in part because we do not have a human-like tissue model for testing,” said Atala. “The development of tissue engineered 3D brain tissue equivalents such as these can help advance the science toward better treatments and improve patients’ lives.”

Scientists at WFIRM have to date used the brain organoids to mimic strokes in order to measure impairment of the blood-brain barrier and have successfully tested the model’s permeability with large and small molecules.

“Just like the invention of the moving assembly line reduced the cost of cars and made them commonplace, the field of regenerative medicine must develop standardized manufacturing processes to successfully make replacement tissues and organs more widely available,” he said.

The $10 million award was given to the WFIRM-founded non-profit RegenMed Development Organization in March 2017 by a public-private partnership involving the U.S. Army Medical Research and Materiel Command. A 40-member consortium founded by WFIRM and made up of not-for-profit organizations, academic, and regenerative medicine industry leaders called Regenerative Manufacturing Innovation Consortium (RegMIC) matched the award. The group's purpose is to help ensure a smooth transition of new therapies to market, which includes working with government agencies to develop standards and address regulatory challenges.

The purpose of Medical Technology Enterprise Consortium (MTEC) is to accelerate progress in regenerative medicine manufacturing.

“Regenerative medicine therapies are already benefiting small groups of patients through clinical trials,” said Atala. “While there is still much to accomplish scientifically, the field is at a tipping point. If we are going to bring high-quality, cost-effective therapies to patients, now is the time to begin the important work of developing the manufacturing processes. Collaboration between industry and academic researchers increases the chance of success."

A long-term goal of the RegMIC is to build a library of proven processes and materials that can be used by researchers and regenerative medicine companies, Atala said, adding that access to this information will help standardize the manufacturing process and help speed up the approval of new therapies.